1. Field of the Invention
The present invention relates to plastic surgical instruments, medical devices, prosthetic cardiovascular implants and implants for hard and soft tissue, contact lenses and the like, and methods for improving surfaces thereof.
2. Prior Art
Studies have shown that the surgical implantation of ocular implants such as intraocular lenses (IOL), etc., results in the loss of significant corneal endothelial tissue unless great care is taken to ensure a lack of contact between the device and the endothelium. Most ocular implants are constructed of hydrophobic polymethylmethacrylate (PMMA) polymers because of their superior optical qualities, resistance to biodegradation, etc. It has been found, however, that PMMA surfaces adhere to endothelial cells upon even casual contact and that separation of the surface therefrom results in a tearing away of the endothelial tissue adhered to the polymer surface. Similar adhesive interactions with other ocular tissues, i.e., the iris, can also cause adverse tissue damage. Other hydrophobic polymers which are used or have been proposed for use in ocular implants (i.e., polypropylene, polyvinylidene fluoride, polycarbonate, polysiloxane) also can adhere to ocular tissue and thereby promote tissue damage.
It is well documented in the prior art that a significant disadvantage inherent in PMMA IOLs resides in the fact that any brief, non-traumatic contact between corneal endothelium and PMMA surfaces results in extensive damage to the endothelium. See Bourne et al, Am. J. Ophthalmol., Vol. 81, pp. 482-485 (1976). Forstor et al, Trans. Am. Acad. Ophthalmol. Otolaryngol., Vol. 83, OP-195-OP-203 (1977); Katz et al, Trans. Am. Acad. Ophthalmol. Otolaryngol, Vol. 83, OP 204-OP-212 (1977); Kaufman et al, Science, Vol. 198, pp. 525-527 (1977) and Sugar et al, Arch. Ophthalmol. Vol. 96, pop. 449-450 (1978) for a discussion of the problem associated with implant surface/endothelium contact.
Since it is extremely difficult to avoid any contact between implant surfaces and endothelium during surgical procedures, efforts have been undertaken to modify the PMMA ocular implant surfaces to reduce the tendency thereof to adhere to and damage corneal endothelium.
Ocular implant surfaces have been coated with various hydrophilic polymer solutions or temporary soluble coatings such as methylcellulose, polyvinylpyrrolidone (Katz et al and Knight et al, supra), etc., to reduce the degree of adhesion between the implant surfaces and endothelial tissue cells. While offering some temporary protection, these methods have not proven entirely satisfactory since such coatings complicate surgery, do not adhere adequately to the implant surfaces, become dislodged or deteriorate after implantation, dissolve away rapidly during or soon after surgery or may produce adverse post-operative complications. Moreover, it is difficult to control the thickenesses and uniformity of such coatings.
Yalon et al [Acta: XXIV, International Congress of Ophthalmology, ed. Paul Henkind (1983)] attempted to produce protective coatings on PMMA implant surfaces by gamma-radiation induced polymerization of vinylpyrrolidone thereon [Se also Knight et al, Chem. Abs., Vol. 92: 203547f (1980]. Their efforts were not altogether successful, however, since their methods also presented problems in controlling the optical and tissue protective qualities of the coatings. Process conditions and parameters (i.e., monomer concentration solvent, dose and dose rate) were not specified. The resulting coating were of poor quality and non-uniform mechanical stability.
Gamma-PVP treatment of PTFE has been reported but under severe process conditions gamma doses above 1 Mrad are impractical in that both bulk and surface properties of the PTFE are changed [Boffa et al., J. Biomed. Mater. Res., 11, 317 (1977]. Non-aqueous solutions of high monomer concentrations (50% NVP in pyridine) are required at relatively high doses of gamma radiation (1-5 Mrad) resulting in a high degree of grafting with extensive changes in the bulk and surface properties of the PTFE since PTFE is readily degraded at gamma doses above 1 Mrad.
In application Ser. No. 037,153, filed Apr. 10, 1987, there are described improved methods for producing hydrophilic, gamma irradiation induced polymerized and chemically grafted coatings on ocular implants constructed of a variety of polymeric materials, which methods overcome the above-noted difficulties and disadvantages.
The invention described in that application is predicated on the discovery of certain process conditions and parameters that produce thin hydrophilic gamma irradiation induced polymerized and chemically grafted coatings of N-vinyl-pyrrolidone (NVP) [PVP], copolymerized NVP and 2-hydroxyethylmethacrylate (HEMA) [P(NVP-HEMA)], or HEMA [PHEMA] on the surfaces of ocular implants constructed of materials including polymethylmethacrylate (PMMA) and of other process conditions and parameters which produce thin gamma irradiation induced graft PVP, P(NVP-HEMA), or PHEMA coatings on the surfaces of ocular articles constructed of materials including polypropylene (PP), polyvinylidene fluoride (PVDF), polycarbonate (PC) and silicone (PSi). The coatings increase the hydrophilicity of the implant surface and minimize adhesion between the surface and sensitive ocular tissues such as corneal endothelium or iris thereby minimizing tissue damage and post-operative complications occasioned by contact between the implant surface and ocular tissue. The coatings produced by the improved method of the invention described in application Ser. No. 037,153 are thin and reproducibly uniform. Moreover, they are chemically bound to the surface of the ocular implant and, therefore, far more durable and less subject to removal, degradation or deterioration during or following surgery than the coatings produced by prior art methods.
The improved gamma-irradiation induced graft polymerization of NVP, HEMA or mixtures of NVP and HEMA on ocular implant surfaces comprising PMMA to form optimum PVP, P(NVP-HEMA) or PHEMA graft polymer surface modifications thereon comprises carrying out the graft polymerization in an aqueous solution under specific combinations of the following conditions:
(a) monomer concentration in the range of from about 0.5 to about 50%, by weight; PA1 (b) total gamma dose in the range of from about 0.01 to about 0.50 Mrad; PA1 (c) gamma dose rate in the range of from about 10 to about 25000 rads/minute; and PA1 (d) maintaining the molecular weight of the polymer in solution in the range of from about 250,000 to about 5,000,000. PA1 (e) substantially excluding free oxygen from the aqueous graft polymerization solution; PA1 (f) maintaining the thickness of the PVP or P(NVP-HEMA) surface graft in the range of from about 100A to about 100 microns; PA1 (g) including a free radical scavenger in the aqueous graft polymerization solution; and PA1 (h) including in the aqueous graft polymerization solution a swelling solvent for PMMA or other polymer substrate surface. PA1 (a) monomer concentration in the range of from about 0.5 to about 50%, by weight; PA1 (b) total gamma dose in the range of from about 0.01 to about 0.50 Mrad; PA1 (c) gamma dose rate in the range of from about 10 to about 25000 rads/minute; and PA1 (d) maintaining the molecular weight of the polymer in solution in the range of from about 250,000 to about 5,000,000. PA1 (e) substantially excluding free oxygen from the aqueous graft polymerization solution; PA1 (f) maintaining the thickness of the PVP or P(NVP-HEMA) surface graft in the range of from about 100A to about 100 microns; PA1 (g) including a free radical scavenger in the aqueous graft polymerization solution; and PA1 (h) including in the aqueous graft polymerization solution a swelling solvent for PMMA or other polymer substrate surface.
Optimally, the method may also be carried out under one or more of the following conditions:
The improved gamma-irradiation induced graft polymerization of NVP, mixtures of NVP and HEMA or HEMA on ocular implant surfaces comprising PP, PVDF, PC or PSi to form optimum PVP or P(NVP-HEMA) surface grafts thereon may also be carried out under specific combinations of the process parameters as indicated above for PMMA but also under conditions which involve excluding free oxygen from the polymerization solution for preferred surface modification of these ocular implant polymer substrates.
At the present time, surgical instruments, medical devices, prosthetic implants, contact lenses and the like which are intended for contact with blood or with sensitive tissue surfaces are constructed of materials having the necessary physical properties to enable their use for the intended application; however, they suffer from the disadvantage that due to the generally hydrophobic nature of the blood or tissue contacting surfaces thereof, they exhibit undesired thrombogenic properties and significant damage is done to fragile or sensitive tissues by adhesion and manipulation or movement on contact with these instruments.
It is therefore an object of the present invention to provide an improved method for producing permanent, thin, uniform, tissue-protective hydrophilic surface modifications of plastic surgical instruments, medical devices, prosthetic implants, contact lenses and the like.
It is a further object of the invention to provide plastic surgical instruments, medical devices, prosthetic implants, contact lenses and the like having improved blood compatible and tissue-protective surface modifications thereon.